US 11,691,984 B2
Compounds and methods for DCAF-mediated protein degradation
Benjamin Cravatt, La Jolla, CA (US); Vincent Crowley, San Diego, CA (US); and Xiaoyu Zhang, San Diego, CA (US)
Assigned to THE SCRIPPS RESEARCH INSTITUTE, La Jolla, CA (US)
Filed by The Scripps Research Institute, La Jolla, CA (US)
Filed on Oct. 11, 2019, as Appl. No. 16/600,326.
Claims priority of provisional application 62/745,076, filed on Oct. 12, 2018.
Prior Publication US 2020/0190105 A1, Jun. 18, 2020
Int. Cl. C07D 495/14 (2006.01); C07B 59/00 (2006.01)
CPC C07D 495/14 (2013.01) [C07B 59/002 (2013.01); C07B 2200/05 (2013.01)] 17 Claims
 
1. A DDB1- and CUL4-associated factor 16 (DCAF16) conjugate comprising a DCAF16 protein covalently bound to a synthetic ligand at a cysteine residue, wherein the cysteine residue is at an amino acid position corresponding to residue 58, 100, 103, 119, 173, 177, 178, or 179 of the amino acid sequence of SEQ ID NO: 1, and wherein the synthetic ligand comprises the structure of Formula (I):

OG Complex Work Unit Chemistry
wherein,
CRG is a bromodomain binder; L is a linker;
MRE is a molecular recognition element that is capable of interacting with DCAF16, wherein the MRE comprises a Michael acceptor moiety capable of forming a covalent bond to the thiol of a cysteine residue in the DCAF16 protein; and RM comprises a binding element that binds to a second protein or another compound.